3DNG
Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor
Summary for 3DNG
| Entry DOI | 10.2210/pdb3dng/pdb |
| Related | 1UTT 1UTZ 1XUC 1XUD 1XUR 2OW9 2OZR |
| Descriptor | Neutrophil collagenase, CALCIUM ION, ZINC ION, ... (5 entities in total) |
| Functional Keywords | hydrolase, selective inhibition, non-zinc chelating inhibitors, calcium, collagen degradation, extracellular matrix, glycoprotein, metal-binding, metalloprotease, polymorphism, protease, secreted, zinc, zymogen |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasmic granule: P22894 |
| Total number of polymer chains | 2 |
| Total formula weight | 37580.43 |
| Authors | Pochetti, G.,Montanari, R.,Mazza, F. (deposition date: 2008-07-02, release date: 2009-03-03, Last modification date: 2023-11-01) |
| Primary citation | Pochetti, G.,Montanari, R.,Gege, C.,Chevrier, C.,Taveras, A.G.,Mazza, F. Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S(1)' Subsite of Matrix Metalloproteinase 8 (MMP-8) J.Med.Chem., 52:1040-1049, 2009 Cited by PubMed Abstract: The mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members. PubMed: 19173605DOI: 10.1021/jm801166j PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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